Adverse Drug Reactions

Question 1

What is an adverse drug reaction?

Answer 1

Any undesirable reaction that results in a detriment to the well being of the patient in any way, in the absence of another biologically plausible explanation

Question 2

What groups are adverse drug reactions most common in?

Answer 2

Elderly or frail, multimorbid and polypharmacy

Question 3

How is the therapeutic index calculated?

Answer 3

TD50/ED50

Question 4

What are some drugs with a narrow therapeutic index and must be used with caution?

Answer 4

Index <2 = theophylline, warfarin, lithium, digoxin, gentamicin, vancomycin, cyclosporin, phenytoin, carbamazepine, levothyroxine

Question 5

When may adverse reactions to a drug bet detected?

Answer 5

Drug development (pre-clinical) = most efficient, least attrition
Clinical trials (phase1-3) = limited sample size, exclusion of frail patients 
Post-marketing surveillance (phase 4 onwards) = less efficient, highest attrition but most data available

Question 6

What are the phases of drug metabolism?

Answer 6

Phase 1 = usually through Cyp P450, oxidation, reduction and hydrolysis
Phase 2 = conjugation, enables excretion in urine/bile

Question 7

What phase of drug metabolism are almost all adverse reactions associated with?

Answer 7

Phase 1

Question 8

What is the classification of adverse drug reactions?

Answer 8

Type A = augmented pharmacological effects
Type B = bizarre effects (idiosyncratic)
Type C = chronic effects
Type D = delayed effects
Type E = end of treatment effects
Type F = failure of treatment

Question 9

What is the difference between type A and type B drug reactions?

Answer 9

Type A is dose dependent and predictable

Type B is dose independent and unpredictable

Question 10

What categories are type A reactions split into?

Answer 10

Pre-renal failure, renal failure and post-renal failure

Drug interactions

Question 11

What are some features of type A pre-renal failure?

Answer 11

Hypovolaemia and hypotension

Drug causes include diuretics and ACE inhibitors/ARBs

Question 12

What are some features of type A renal failure?

Answer 12

AIN/tubular necrosis

May be caused by gentamicin, sulphonamides or aspirin

Question 13

What are some features of type A post-renal failure?

Answer 13

Retroperitoneal fibrosis, crystaluria and urinary calculi

May be due to use of methysergide or chemotherapy

Question 14

What are the different types of drug interactions?

Answer 14

Drug-drug reactions
Drug-disease reactions
Drug-food reactions

Question 15

What are some examples of some common drug-drug interactions?

Answer 15

Statins and macrolides
Clopidogrel and PPIs
Warfarin and many drugs
ACE inhibitors increase effects of sulphonylureas

Question 16

What are some common herbal remedies that may cause drug-drug interactions?

Answer 16

Grapefruit juice (Cyp P450) for vitamin C
Gingko biloba (anticoagulant) for dementia
Saw palmetto (anticoagulant) for BPH
Glucosamine (hyperglycaemia, anticoagulant) for OA

Question 17

What are some common drug-disease interactions?

Answer 17

NSAIDs and COX-2 can exacerbate CHF
Urinary retention in BPH patients on decongestants
Constipation worsened by calcium channel blockers
Beta blockers and asthma

Question 18

What are some examples of foods rich in K+?

Answer 18

Bananas, oranges, green leafy vegetables

Interact with ACE inhibitors, ARBs and K+ sparing diuretics

Question 19

What are some examples of foods that can interact with warfarin?

Answer 19

Rich in vitamin E and K = apples, chickpeas, spinach, nuts, kiwi, broccoli

Question 20

What are some foods that can alter pH to cause drug interactions?

Answer 20

Chicken, turkey, milk, soy, cheese, yogurt

Interact with antibiotics, thyroid medications, digoxin and diuretics

Question 21

What are some foods that contain cytochrome P450?

Answer 21

Grapefruit, apple, orange, cranberry

Interact with statins and anti-histamines

Question 22

What are some examples of type B reactions?

Answer 22

Drug rashes, bone marrow aplasia, hepatic necrosis = higher mortality

Question 23

What causes type C reactions?

Answer 23

Due to prolonged therapy = can be anticipated but patient must be warned before starting therapy

Question 24

What are some examples of type C reactions?

Answer 24

Steroids cause Cushing’s
Beta blockers cause diabetes
NSAIDs cause hypertension

Question 25

When do type D reactions tend to occur?

Answer 25

Remote from treatment = usually many years after stopping

Question 26

What are some features of type D reactions?

Answer 26

Devastating = teratogenic or carcinogenic effects

Less frequent now due to rigorous pre-clinical testing

Question 27

What cause type E reactions?

Answer 27

Abrupt withdrawal of drug = causes rebound effects

Question 28

What are the two mechanisms of type E reactions?

Answer 28

Loss of physiological coping = beta blocker withdrawal and angina
Mechanism-dependent biological activity = steroid withdrawal and Addisonian crisis

Question 29

What can the black triangle status be applied to?

Answer 29

New medicines that have a new active ingredients
Biologics or vaccines
Licensing requirements

Question 30

When can the black triangle status of a drug be reviewed?

Answer 30

After 2 years = only removed when safety is established

Question 31

When is a yellow card filled in?

Answer 31

Legal requirement = must fill in when patient has an unexpected side effect (even if only suspected)

Question 32

What are the top reported drug for unexpected side effects in Scotland?

Answer 32

Meningococcal B vaccines
Apixaban
Warfarin
Rivaroxaban